Relationship between ganglioside expression and anti-cancer effects of the monoclonal antibody against epithelial cell adhesion molecule in colon cancer.
10.3858/emm.2011.43.12.080
- Author:
Dong Hoon KWAK
1
;
Jae Sung RYU
;
Chang Hyun KIM
;
Kisung KO
;
Jin Yeul MA
;
Kyung A HWANG
;
Young Kug CHOO
Author Information
1. Center for Herbal Medicine Improvement Research, Korea Institute of Oriental Medicine, Daejeon 305-811, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
antibodies, monoclonal;
apoptosis;
colon neoplasms;
EPCAM protein, human;
gangliosides;
macrophages
- MeSH:
Animals;
Antibodies, Monoclonal/*immunology/*therapeutic use;
Antigens, Neoplasm/*immunology;
Apoptosis/drug effects;
Cell Adhesion Molecules/*immunology;
Cell Line;
Cell Line, Tumor;
Cell Proliferation/drug effects;
Colon/drug effects/immunology/metabolism/pathology;
Colonic Neoplasms/*drug therapy/genetics/*immunology/pathology;
Gangliosides/genetics/*immunology;
Gene Expression Regulation, Neoplastic/drug effects;
Humans;
Male;
Mice;
Mice, Inbred BALB C
- From:Experimental & Molecular Medicine
2011;43(12):693-701
- CountryRepublic of Korea
- Language:English
-
Abstract:
The human colorectal carcinoma-associated GA733 antigen epithelial cell adhesion molecule (EpCAM) was initially described as a cell surface protein selectively expressed in some myeloid cancers. Gangliosides are sialic acid-containing glycosphingolipids involved in inflammation and oncogenesis. We have demonstrated that treatment with anti-EpCAM mAb and RAW264.7 cells significant inhibited the cell growth in SW620 cancer cells, but neither anti-EpCAM mAb nor RAW264.7 cells alone induced cytotoxicity. The relationship between ganglioside expression and the anti-cancer effects of anti-EpCAM mAb and RAW264.7 was investigated by high-performance thin-layer chromatography. The results demonstrated that expression of GM1 and GD1a significantly increased in the ability of anti-EpCAM to inhibit cell growth in SW620 cells. Anti-EpCAM mAb treatment increased the expression of anti-apoptotic proteins such as Bcl-2, but the expression of pro-apoptotic proteins Bax, TNF-alpha, caspase-3, cleaved caspase-3, and cleaved caspase-8 were unaltered. We observed that anti-EpCAM mAb significantly inhibited the growth of colon tumors, as determined by a decrease in tumor volume and weight. The expression of anti-apoptotic protein was inhibited by treatment with anti-EpCAM mAb, whereas the expression of pro-apoptotic proteins was increased. These results suggest that GD1a and GM1 were closely related to anticancer effects of anti-EpCAM mAb. In light of these results, further clinical investigation should be conducted on anti-EpCAM mAb to determine its possible chemopreventive and/or therapeutic efficacy against human colon cancer.
